Regulatory Omics Databasefor Analyzing Transcriptional Consequences of Human SNVs

ABSTRACT〇Yutaka Suzuki1, Hiroyuki Wakaguri2, Riu Yamashita3, Shin Kawano4, Katsuya Tsuchihara5,
Kenta Nakai6 and Sumio Sugano1
1Department of Medical Genome Sciences, Graduate School of Frontier Sciences, The University of Tokyo,
2Department of Computational Biology, Graduate School of Frontier Sciences, The University of Tokyo,
3Tohoku Medical Megabank Organization, Tohoku University, Miyagi, Japan,
4Database Center for Life Science, Research Organization of Information and Systems, Chiba,
5Division of TR, The Exploratory Oncology Research and Clinical Trial Center, National Cancer Center, Chiba
6Human Genome Center, The Institute of Medical Science, The University of Tokyo

DBTSS (http://dbtss.hgc.jp/) was originally constructed as a collection of uniquelydetermined transcriptional start sites (TSSs) in humans and some other species in2002. Since then, it has been regularly updated and in recent updates epigenetic
information has also been incorporated because such information is useful forcharacterizing the biological relevance of these TSSs/downstream genes. In the newest
release, Release 9, we further integrated public and original single nucleotide
variation (SNV) data into our database. For our original data, we generated SNV datafrom genomic analyses of various cancer types, including 97 lung adenocarcinomas
and 57 lung small cell carcinomas from Japanese patients as well as 26 cell lines oflung cancer origin. In addition, we obtained publically available SNV data from othercancer types and germline variations in total of 11,322 individuals. With these updates,
users can examine the association between sequence variation pattern in clinical lungcancers with its corresponding TSS-seq, RNA-seq, ChIP-seq and BS-seq data.
Consequently, DBTSS is no longer a mere storage site for TSS information but has
evolved into an integrative platform of a variety of genome activity data.
Reference:-Suzuki A, Wakaguri H, Yamashita R, Kawano S, Tsuchihara K, Sugano S, Suzuki Y,
Nakai K. DBTSS as an integrative platform for transcriptome, epigenome andgenome sequence variation data. Nucleic Acids Res. 2014 Nov 5. pii: gku1080. [Epubahead of print]-Suzuki A, Makinoshima H, Wakaguri H, Esumi H, Sugano S, Kohno T, Tsuchihara K,Suzuki Y. Aberrant transcriptional regulations in cancers: genome, transcriptome
and epigenome analysis of lung adenocarcinoma cell lines. Nucleic Acids Res. 2014
Nov 6. pii: gku885. [Epub ahead of print]

Data Contents of the KERO (Summary)

Data Contents of the KERO (Human SNVs)

Kashiwa Encyclopedia of Regulatory Omics (KERO@http://dbtss.hgc.jp/)

Search Example of KERO (TSS)AB

C

Top page of KERO.
A simple search for‘TSS Viewer’ and‘Genome Viewer’ canbemadebyspecifying a keyword,such as a gene name
‘BRAF’intheDatabase Search atthe left frame (redbox). Search by‘SNV Summary inCancers’and‘Pathway Map’ canbe made from thepositions indicated byorange and purple
boxes, respectively.

Figure 1 DBTSS Browser(A) A part of the TSS Viewer display for the BRAF gene. The overview and the detailed positions of the TSSs are shown in the upper and lower panels,respectively. Many of the fields are expandable. (B) The default display of Genome Viewer for the BRAF gene. Displayed items are as indicated in themargin. The displayed items can be controlled from the panels located under the ‘Select track items’ headline. (C) A sample output of SNV information for
the BRAF gene. Surrounding region of a previously reported cancer driver mutation (V600E of the BRAF gene; highlighted in red box), is displayed.

RDF for Integration of the Databases

AB

Figure 2 Pathway Searchand Promoter Search(A) Upper panel: A part of theMutation frequency table for
the BRAF gene. Enrichedfields are as highlighted;
lower panel: Summary ofmulti-omics
datamainlycollected from cell lines. (B)Pathway Map representationof characteristic genes. In thisexample, gene expression
level (in RPKM) of nodegenes
inalung
adenocarcinoma cell line,
LC2/ad, in the ErbB/HER
signaling pathway is shown.
Further links will appear when
the users click the circle
corresponding to each gene.

Figure 3 Schema for RDF of ChIP data

All contents and raw data freely downloadable from DBTSS at:
http://dbtss.hgc.jp

Licensed under a Creative Commons表示4.0国際(c)2016 Yutaka Suzuki （Graduate School of Frontier Sciences, TheUniversity of Tokyo）